Biomedical subjects

K Miyai

Publications and source records attributed to K Miyai.

At least 127 records · Page 7Linked to original sources

PubMed1989

Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit.

Congenital isolated thyroid-stimulating hormone (TSH) deficiency is an autosomal recessive disease that manifests as hypothyroidism (cretinism), causing severe mental and growth retardations. Patients were found to have a single base substitution in the codon for the 29th amino acid of the TSH beta subunit gene. The alteration is in the center of the so-called CAGYC region, which consists of an amino acid sequence conserved among all of the known glycoprotein hormone beta subunits. No other nucleotide substitutions have been found in the gene thus far sequenced. Microinjection of the mutated beta mRNAs into Xenopus laevis oocytes led to the formation of conformationally altered beta polypeptides that could not associate with alpha subunits. The mutation created a new recognition site for the enzyme MaeI. Southern blot hybridization of genomic DNA digested with MaeI showed that the patients were homozygous and their parents were heterozygous for the mutation. This test was also used to examine other family members for the disease.

Amino Acid Sequence↗

PubMed1989

Effects of propylene glycol on redox state of the perfused rat liver--a note of caution.

Propylene glycol is used as a solvent for bile salts in studies on their biologic effects on the liver. While using this solvent (32-64 mmol/l) in the isolated perfused rat liver, we found a significant change in the extramitochondrial redox system as indicated by a fivefold increase of the lactate pyruvate ratio in the perfusate. The increase was due to an increased uptake of pyruvate (0.8 mumol/g/min) and to a release of lactate (1.8 mumol/g/min). The intramitochondrial redox state was affected to a lesser degree as estimated by the beta-hydroxybutyrate acetoacetate ratio (twofold increase). These abnormalities resemble those induced by similar concentrations of ethanol. We suggest, therefore, that investigators studying bile acids should be aware of this artifact which causes significant alterations in cellular energy systems and enzyme activities.

3-Hydroxybutyric Acid↗

PubMed1989

Improvement of infiltrative ophthalmopathy in parallel with decrease of thyroid-stimulating antibody (TSAb) activity in two patients with hypothyroid Graves' disease.

Two patients with primary hypothyroidism associated with infiltrative ophthalmopathy without previous history of hyperthyroidism are presented. Anti-TSH receptor antibodies (TRAb) were detected by radioreceptor assay (TBII), and unexpectedly their biological activity was not of a blocking (TSBAb), but of a thyroid-stimulating type (TSAb). After the initiation of levothyroxine therapy, the TBII and TSAb activities both decreased gradually with normalization of the elevated TSH level. The inflammatory eye signs improved strikingly in parallel with decrease of these antibody activities. These data indicate that (1) TRAb in primary hypothyroidism do not always show TSAb activity, (2) the decrease in TRAb following levothyroxine therapy in these patients appeared to correlate with suppression of TSH, (3) changes in infiltrative ophthalmopathy were associated with that of TSAb even in primary hypothyroidism, and (4) the hypothyroidism in these patients is justifiably diagnosed as "hypothyroid Graves' disease". TSAb might be somewhat related to the pathogenesis of ophthalmopathy in autoimmune thyroid diseases.

Antibodies↗

PubMed1989

Intrathyroidal HLA-DR-positive lymphocytes in Hashimoto's disease: increases in CD8 and Leu7 cells.

The peripheral and intrathyroidal HLA-DR-positive (DR+) lymphocyte subsets that were activated in vivo in patients with Hashimoto's disease (HD) were examined by two-color flow cytometry with monoclonal antibodies against CD3, CD4, CD8, Leu7, CD19, and HLA-DR antigens. The proportions of total DR+ cells in peripheral lymphocytes and the proportions of DR+ cells in the CD3+, CD4+, and Leu7+ lymphocytes were higher in patients with HD than in normal controls. Furthermore, the proportions of total DR+ cells among intrathyroidal lymphocytes isolated from thyroid tissue of individuals with HD were higher than those in their peripheral lymphocytes. Interestingly, the proportions of DR+ cells among the CD3+, CD8+, and Leu7+ lymphocytes in the thyroid were greatly increased. These data indicate that (i) CD3+ T, especially CD4+ T helper/inducer, lymphocytes and Leu7+ NK/K cells are activated in peripheral blood in Hashimoto's disease and that (ii) CD3+ T, especially CD8+ T suppressor/cytotoxic, lymphocytes and Leu7+ NK/K cells are predominantly activated in Hashimoto's goiter, suggesting an increase of cell-mediated cytotoxicity in the thyroid in Hashimoto's disease.

Adult↗

PubMed1989

Peripheral large granular lymphocytes in normal pregnant and postpartum women: decrease in late pregnancy and dynamic change in the puerperium.

Large granular lymphocytes (LGLs) have a variety of cytotoxic activities of NK, K and cytotoxic T lymphocytes, suggesting that their morphology is indicative of lytic function. In non-pregnant normal control women (n = 48), the number of LGLs was 0.30 +/- 0.14 x 10(9)/l and the proportion of LGLs in their peripheral lymphocyte fraction was 14.0 +/- 5.4%. The number and proportion of LGLs were significantly decreased in the third trimester of pregnancy (n = 32; 0.19 +/- 0.08 x 10(9)/l, P less than 0.01, and 11.7 +/- 3.8%, P less than 0.05), although an unexpected increase in the proportion of LGLs was observed in the first trimester of pregnancy (n = 24; 17.5 +/- 6.5%, P less than 0.05). After delivery, the number and proportion of LGLs increased rapidly to restore the non-pregnant levels and showed a marked increase in LGL count 4 months postpartum. These data suggest that lymphocyte-mediated cytotoxicity decreases in late pregnancy and increase dynamically after delivery to restore the non-pregnant state.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1989

Peripheral K cells in normal human pregnancy: decrease during pregnancy and increase after delivery.

Peripheral blood levels of K cells were measured in normal pregnant and post-partum women by a plaque-forming cell technique that detects K cells on the basis of their activity of antibody-dependent cell-mediated cytotoxicity (ADCC). Peripheral K cells decreased throughout normal pregnancy (n = 46; 7.8 +/- 3.4%, P less than 0.01; 0.13 +/- 0.08 X 10(9)/l, P less than 0.001) and increased in the post-partum period (n = 17; 14.2 +/- 6.1%, P less than 0.05; 0.32 +/- 0.20 X 10(9)/l, P less than 0.01) in comparison with those in normal non-pregnant controls (n = 29; 10.5 +/- 4.2%; 0.20 +/- 0.09 X 10(9)/l). These findings suggest that a decrease of K cells during pregnancy may contribute in part to maternal acceptance of the fetal allograft and that the post-partum increase of K cells may represent a post-partum increase of cell-mediated cytotoxicity, which may contribute to natural defense against puerperal infection.

Adult↗

PubMed1989

Peripheral self-tolerance and autoimmunity: the protective role of expression of class II major histocompatibility antigens on non-lymphoid cells.

Immunologic self-tolerance is achieved mainly during development by clonal deletion in the thymus of T lymphocytes with receptors specific for self-antigens and with associated T-cell markers CD4/CD8. However, T cells expressing a low level of these markers are allowed into the periphery still bearing their autospecific receptors. Such clonal deletion, induced by cells bearing the class II antigens coded for by major histocompatibility complex (MHC) in the thymus, does not remove all autoreactive T cells specific for antigens of differentiated tissue expressed extrathymically. However, these autoreactive T cells are silent in the periphery. Peripheral non-lymphoid cells (e.g., endocrine cells) can induce antigen-specific unresponsiveness in T cells and can specifically suppress production of autoantibody against their antigens when the non-lymphoid cells express class II MHC antigens on their surface. This class II MHC expression is induced by interferon-gamma produced by T cells as a result of various immune responses, such as autoimmune reaction. Thus, the expression of class II MHC antigens on non-lymphoid cells may serve as a peripheral mechanism for the induction and maintenance of self-tolerance in autoreactive T cells that escape negative selection in the thymus or that are specific for extrathymic tissue antigens, in a fail-safe mechanism against autoimmunity. Some autoimmune diseases, especially organ-specific ones, might be caused by a defect in this fail-safe mechanism.

Autoimmune Diseases↗

PubMed1989

Effective method for prediction of transient hypothyroidism in neonates born to mothers with chronic thyroiditis.

An effective method of prediction of neonatal transient hypothyroidism was examined in 105 neonates (including a pair of twins) born to mothers with chronic thyroiditis (92 mothers with goitrous Hashimoto's disease and 12 with primary atrophic hypothyroidism). Antithyroid microsomal antibody was measured by a hemagglutination technique (MCHA), and antithyroid-stimulating hormone (TSH) receptor antibody by both radioreceptor assay (TBII) and biologic thyroid-stimulation blocking assay (TSBAb). For generalization of predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of MRC-LATS-standard B as a reference, and that of TSBAb activity was standardized as the degree of dilution with normal pooled serum to attain 50% inhibition of TSH (100 microU/ml)-induced cyclic adenosine monophosphate increase (TSBAb50). The MCHA titer in maternal serum at delivery correlated well with that of the corresponding cord serum, but not with the free thyroxine (T4) index or the TSH level in cord serum. TBII activity was positive in only 4 of 12 mothers with primary atrophic hypothyroidism, TSBAb activity was also positive only in these four mothers, and neonatal thyroid dysfunction was observed in three of their neonates. Two of these neonates developed transient hypothyroidism requiring T4 treatment, and the t third developed mild transient hyperthyrotropinemia with normal T4 and triidothyronine levels. The mothers whose neonates showed transient hypothyroidism had TBII activities of more than 300 U/ml and TSBAb50 activities of more than 300. Ninety-two mothers with goitrous Hashimoto's disease had neither TBII nor TSBAb activity, irrespective of their thyroid function, and delivered euthyroid babies.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1989

Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease.

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.

Antibodies↗

PubMed1989

Transient infantile hyperthyrotrophinaemia.

Sixteen cases of transient infantile hyperthyrotrophinaemia were followed up for two to seven years. Concentrations of serum triiodothyronine, thyroxine, and free thyroxine were maintained within the normal range in all cases. All but one child, who had a hearing disturbance, showed normal mental development with normal physical and skeletal maturation. Eleven children had normal concentrations of serum thyroid stimulating hormone and no signs or symptoms of thyroid dysfunction; in three children, diffuse small goitres developed and two further children showed relapse with slightly raised concentrations of thyroid stimulating hormone. It is concluded that 'transient infantile hyperthyrotrophinaemia' is a syndrome, which differs from typical transient neonatal hypothyroidism, and that careful follow up is necessary because some children show signs of mild pituitary-thyroid dysfunction in later childhood.

Child Development↗

PubMed1989

Effect of food on nifedipine sustained-release preparation.

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (Cmax) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng.h/mL, and the mean Cmax were 42.6 and 86.6 micrograms/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

Adult↗

PubMed1989

Analysis of overall pathophysiological relationships between serum levels of TSH and thyroid hormones using a large laboratory database.

Factors associated with the basal level of serum thyrotropin (TSH) were analyzed over a wide range of pathophysiological conditions by means of a large laboratory database on thyroid function. When data were analyzed two-dimensionally, serum TSH showed significant inverse correlations with total triiodothyronine (T3), free T3 index (FT3I), total thyroxin (TT4) and free T4 index (FT4I) in the order of increasing intensity. The three-dimensional analysis, however, revealed that 1) total hormone levels were actually unrelated to serum TSH when the levels of free hormone indices were held constant, 2) the relation between FT3I and TSH became obscure when the influence of FT4I was similarly removed. On the other hand, 3) the relation of FT4I with TSH was unaffected by the level of FT3I. These results suggest that free T4 is the main determinant of the serum TSH level. This study also implies that it is possible to use large amounts of laboratory data to elucidate the overall profile of a given patho-physiological system, whose structure is only partially revealed by conventional clinical or animal studies.

Data Interpretation, Statistical↗

PubMed1989

Incidences of antibodies to Yersinia enterocolitica: high incidence of serotype O5 in autoimmune thyroid diseases in Japan.

Antibodies to Yersinia enterocolitica serotype O3, O5, O6 and O9 were measured by the micro-agglutination method in 445 healthy subjects and patients with Grave's disease (n = 70), Hashimoto's disease (n = 45) and thyroid tumor (n = 29). In contrast to previous reports, the incidence of antibodies to serotype O3 in each group of patients with thyroid diseases was not significantly different from that in healthy subjects. However, the incidence of antibodies to serotype O5 was significantly higher in patients with Graves' disease (81.4%, P less than 0.001) and Hashimoto's disease (91.1%, P less than 0.001) than in healthy subjects (258.9%). Significantly increased incidence of antibodies to serotypes O6 and O9 was observed only in patients with Hashimoto's disease (40.0% and 51.1% vs healthy subjects 24.7% and 29.9%, respectively). Patients with thyroid tumor showed no increase in any serotype of Yersinia enterocolitica. No correlations was found between the titers of anti-Yersinia antibodies and anti-thyroglobulin or anti-microsomal antibodies. These data indicate an association between thyroid autoimmunity and antibodies to Yersinia enterocolitica. These results are different from those in reports from other countries, suggesting that serotype specificity may be influenced by racial or genetic factors.

Antibodies, Bacterial↗

PubMed1989

Enzyme immunoassay for oxytocin.

A competitive, double antibody enzyme immunoassay for oxytocin in a heterologous system was developed. Horseradish peroxidase was conjugated with oxytocin using N-succinimidyl 3-(2-pyridyldithio) propionate, and rabbit anti-oxytocin serum was produced by immunization of oxytocin-bovine serum albumin complex which was prepared by the carbodiimide method. The sensitivity of the assay was 4 microIU/tube, which corresponded to 10 microIU per ml using 400 microliters of the sample which was extracted from the same volume of plasma by means of SEP-PAK C18 cartridges. The coefficients of variation for different levels of oxytocin ranged from 6.8-15.9% and 8.5-16.7%, for intra- and inter-assay. Recovery of oxytocin added to plasma after extraction was 99-117%. No or little cross-reaction with arginine- and lysine-vasopressin was found. Plasma oxytocin concentrations determined by the proposed enzyme immunoassay were well correlated with those determined by radioimmunoassay (r = 0.90).

Immunoenzyme Techniques↗

PubMed1989

Subacute thyroiditis associated with systemic multi-organ disorders.

Subacute thyroiditis is generally thought to be a self-limited inflammatory disease of the thyroid gland. This paper describes serial observations on the clinical course of a typical patient with subacute thyroiditis. This patient showed specific features of destructive thyrotoxicosis with increases in the serum levels of acute phase reactants and in the erythrocyte sedimentation rate. She also showed signs of liver dysfunction [slightly increased alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP), and leucine aminopeptidase (LAP)], slight anemia, glucose intolerance, increased pancreatic enzymes, splenomegaly, and an increase in peripheral Leu 7 positive (NK/K) cells. These abnormalities all improved with recovery from disease. These findings indicate that in this patient with subacute thyroiditis inflammation is not limited to the thyroid gland but also involves the liver, pancreas and spleen. Thus the subacute thyroiditis in this patient may be a systemic multi-organ disease.

Female↗

PubMed1989

Epitope mapping of human thyrotropin.

Epitope mapping of hTSH was carried out using 19 monoclonal antibodies prepared with hTSH or its beta-subunit as antigen. The affinity constants of the monoclonal antibodies ranged from 9.6 X 10(7) to 5.7 X 10(9) mol/l for hTSH. The binding activities of monoclonal antibodies were maintained or in some cases rather enhanced after removal of the sugar moiety of the subunits of hTSH, and completely diminished after reduction of intramolecular S-S bonds in the subunits of hTSH. Ten monoclonal antibodies recognized the epitopes on hTSH (alpha:beta subunit combined form) and on free alpha-subunit form. Eight other antibodies recognized the epitopes on free/or combined form of beta-subunit, all of which did not recognize any other human glycoprotein hormones. The monoclonal antibodies directed against the alpha-subunit could bind also other human glycoprotein hormones to a varying extent. On the basis of results from competitive binding studies, the antibodies directed against alpha-subunit and those against beta-subunit were each classified into five subgroups recognizing different antigenic determinants. The remaining one antibody recognized an epitope expressed only by hTSH and not by the free subunits. In addition, a positive cooperativity on the binding of hTSH was observed between monoclonal antibodies directed towards a particular epitope on the alpha-subunit and those towards a epitope on the beta-subunit. From these data, two-dimensional map of epitopes on hTSH was constructed. The epitopes on each subunit were found to form a cluster with complicated overlapping, suggesting a highly conformational structure.

Animals↗

PubMed1989

Marked increase of CD5 + B cells in hyperthyroid Graves' disease.

We examined the proportions of B lymphocytes bearing CD5 cell surface antigen (CD5+ B cells), which are capable of making autoantibodies, in peripheral blood from patients with various thyroid diseases. The level of CD5+ B cells was markedly increased (>9.0%) above the normal range (0.5-7.7%) in untreated, hyperthyroid patients with Graves' disease, although about 10% of the patients had no detectable serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb). However, the levels of CD5+ B cells were normal in untreated patients with destructive thyrotoxicosis due to aggravation of Hashimoto's thyroiditis or subacute thyroiditis. In patients with stimulated hyperthyroid Graves' disease the levels of CD5+ B cells were correlated with those of thyroid hormones and TRAb, all significantly increased. However, once hyperthyroidism was controlled by anti-thyroid drugs, CD5+ B cells were decreased, followed in turn by reduction of TRAb. We conclude that the proportion of CD5+ B cells is useful as a therapeutic index and for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis.

Adult↗

PubMed1989

Discordant changes in serum anti-TSH receptor antibody and antithyroid microsomal antibody during pregnancy in autoimmune thyroid diseases.

Immunological effect of pregnancy on the level of anti-TSH receptor antibody (TRAb) and antithyroid microsomal antibody (MCAb) was examined serially in twelve patients; ten with active Graves' disease treated with antithyroid drugs for some time during pregnancy, one with previous Graves' disease with stimulating type TRAb, and one with primary atrophic hypothyroidism with blocking type TRAb. TRAb was measured by radioreceptor assay (TSH-binding inhibitor immunoglobulin, TBII) and MCAb was determined by radioimmunoassay. Among the ten patients with active Graves' disease, TBII level decreased as pregnancy progressed in seven but increased during pregnancy in three, whereas MCAb level decreased uniformly during pregnancy in all ten patients. However, possible immunosuppressive effect of antithyroid drugs on these antibody levels could not be completely excluded in these patients. On the other hand, in the two consecutive pregnancies of the patient with previous Graves' disease, TBII level increased "spontaneously" to 10-fold the initial value at 30 weeks during the first pregnancy, while it did not show consistent increase or decrease during the second one. Another patient with primary hypothyroidism showed increase in TBII level during pregnancy to 5-fold the initial value at week 28. In contrast to these TBII changes, MCAb levels and immunoglobulin concentrations decreased consistently during pregnancy in these two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗